Kane K F, Langman M J, Williams G R
Department of Medicine, University of Birmingham, Edgbaston.
Gut. 1995 Feb;36(2):255-8. doi: 10.1136/gut.36.2.255.
Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy.
流行病学研究表明，1,25 - 二羟基维生素D3（D3）可预防结直肠癌的发生。动物和体外研究显示，D3对包括大肠来源肿瘤在内的多种肿瘤具有抗增殖作用。在所有对D3有反应的组织中，D3的作用由D3受体（VDR）单独介导，或由VDR与视黄酸X受体（RXRs）共同介导。我们测定了正常和恶性人类结肠组织中编码VDR和RXRs的mRNA的表达情况。全长VDR（4.6 kB）、RXRα（5.5 kB）和RXRγ（3.5和7 kB）的mRNA在所有组织中均有表达，但RXRβ的mRNA在任何组织中均未表达。与配对的正常黏膜相比，12例癌组织中的VDR表达降低，9例癌组织中的RXRα表达降低。VDR或RXRα的表达与肿瘤的部位、分化程度或Dukes分期之间无相关性。在所有结直肠癌肿瘤中持续存在VDR和RXR共表达这一发现，为探索D3在结直肠癌治疗中的作用提供了合理依据。
